T cell antigen Recognition. Role of MHC

Question 1

what is a major difference between BCR and TCR?

Answer 1

TCR cannot recognize free antigen (unprocessed). It can only recognize processed
antigen epitope in the form of a small linear peptide presented to it by antigen presenting cells (APCs, macrophages and dendritic cells) via MHC

Question 2

what are the two major classes of TCR?

Answer 2

α, β TCR and the γ, δ TCR

Question 3

what are very efficient as APCs due to their large surface areas and multiple appendages?

Answer 3

dendrites

Question 4

what is the CD8+ T cell MHC class I restricted relationship?

Answer 4

MHC class I molecule on a macrophage is expressing a linear peptide to a TCR on a T cell that co-expresses a CD8 molecule that is associated with the MHC

Question 5

what is the result of activation of aïve CD8+ T cell?

Answer 5

memory CD8+ T cells and effector CD8+ T cells, the cell killers

Question 6

true or false: CD8+ T cells are labeled as intracellular killer cells

Answer 6

false: extracellular

Question 7

what is the function of CD8+ T cells?

Answer 7

target abnormal cells and kill them

Question 8

all nucleated cells express MHC class 1 molecules, why is this important?

Answer 8

This allows the CD8+ T cells to scan any nucleated cell looking for abnormal cells.
These “abnormal cells” are typically viral or bacterial infected cells or cancer cells

Question 9

how do viral-infected cells and cancer cells try to hide from the CD8+ T cells?

Answer 9

by downregulating or altering the expression of the MHC class I molecule preventing foreign antigen peptide presentation

Question 10

what does the innate extracellular killer, NK, do to combat viral or cancer cells hiding?

Answer 10

screens for the presence and structure of the MHC class I molecule on the surface of nucleated cells. If it is absent or defective, the NK cells also destroy the abnormal cell by apoptosis

Question 11

what is the difference between CD4+ T cell MHC Class II restricted and CD8+ T cell
MHC Class I restricted?

Answer 11

naïve CD4+ T cells when activated yield memory CD4+ T cell and effector CD4+ T cells that either interact with B cells to guide isotype-switching or produce a number of different cytokines that help regulate an immune response

Question 12

what expresses MHC class II molecules?

Answer 12

APC (macrophages, dendritic and select B cells)

Question 13

true or false: the APCs express both MHC class I and MHC class II molecules on their surfaces.

Answer 13

true

Question 14

why is tissue typing of the HLA critical for organ transplants?

Answer 14

each individual’s MHC class I and class II molecules can differ from another individual.

Question 15

where can differences in MHC between different individuals in the same species can arise from?

Answer 15

multiple genes (polygenicity) or the genes can exist as multiple stable forms (polymorphisms)

Question 16

what are the molecules that are independent genes found on chromosome 6 that code for the MHC class I?

Answer 16

HLA-A, HLA-B, HLA-C

Question 17

Unique to the MHC class I molecule is a bound molecule called ________________ that is coded for independent of the HLA complex on chromosome 15

Answer 17

β2-microglobulin

Question 18

what are MHC class II molecules are coded for by?

Answer 18

HLA-DP, HLA-DQ and HLA-DR.

Question 19

Variation within a gene can translate to a _________________ different protein coded by that gene, which is the definition of polymorphism

Answer 19

phenotypically

Question 20

why is it that the more ethnically and racially different two individuals are the greater the difference in their HLA proteins and the poorer they are a match for a tissue transplant?

Answer 20

Of all the gene complexes in the body that code for proteins, the MHC complex has most highly polymorphic genes and thus the greatest variation in the HLA proteins that are produced

Question 21

true or false: Since the writing of this book, HLA-DM and HLA-DO have been also described on MHC class II molecules in increasing the number from 6 to 10 possible combinations accounting for variation from both parental chromosomes.

Answer 21

true

Question 22

when does MHC class I molecule present foreign antigen?

Answer 22

when the host ‘s immune system deems detrimental to the cell.

Question 23

why are the α1 and α2 regions classified as the variable region and the remaining region is classified as the invariant region?

Answer 23

the highly variable α1 and α2 regions of the α heavy chain forms the peptide-binding groove unique to each MHC class I molecule.

Question 24

regarding MHC class I, is what determines the structural conformation of the peptide-binding groove and how are the peptides to be presented and selected?

Answer 24

Most of the variation in the amino acid sequences are localized to the α1 and α2
regions, which impact the conformation of the walls and floor of the binding groove. In
addition, the variable amino acid sequences create gaps or pockets in the floor that impact the selection of the linear peptide as well as its alignment in the binding groove to facilitate
presentation to the T cell

Question 25

what does the peptide contain that align with allelic-specific gaps or pockets of each α1 and α2 region?

Answer 25

anchor residues

Question 26

what is the significance of the presence or absence of anchor residues?

Answer 26

determine whether a linear peptide will or will not be selected for presentation to the T cell

(also that the seating of the anchor residues in the pockets ensures a stable presentation of the linear peptide to the T cell)

Question 27

what is the primary function of MHC class II molecule?

Answer 27

present processed antigen in the form of a linear peptide to CD4+ helper T cells to increase in immune response

Question 28

what are the α1and β1 regions of the MHC class II molecule classified as?

Answer 28

variable regions

Question 29

what are α2 and β2

Answer 29

invariant regions

Question 30

Upon binding of the TCR to linear peptide
presented by MHC class II, the CD4 cell surface protein on the T cell binds to the invariant __ region

Answer 30

β2

Question 31

Given MHC class II molecule’s larger size based on molecular weight, it presents with a larger binding groove and thus, can accommodate linear peptides consisting of ______ amino acids in length

Answer 31

12-17

Question 32

the linear peptides associated with the MHC class I molecule range between ______ amino
acids in length.

Answer 32

8-10

Question 33

how does MHC class II molecule select for linear peptides to present to TCR?

Answer 33

1. the linear peptides need to contain anchor residues (3-4) that can structurally bind to the
   allelic-specific pockets located within the peptide-binding groove. This allows for greater
   variability of the remaining amino acids not functioning as anchor residues yield a much larger and diverse pool of linear epitopes for recognition by the TCR.
2. the anchoring of the peptide to the binding groove provides structural stability of the linear peptide.

Question 34

what is MHC restriction?

Answer 34

TCR recognizing the structural confirmation
of the linear peptide that is presented via the MHC on the APC.